ArticleGenes & development2014
ATR checkpoint kinase and CRL1βTRCP collaborate to degrade ASF1a and thus repress genes overlapping with clusters of stalled replication forks.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart.The EMBO journal · 2023Article
- Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription-replication conflicts caused by replication stress.Nucleic acids research · 2022Article
- Walking a tightrope: The complex balancing act of R-loops in genome stability.Molecular cell · 2022Review
- Downregulation of ASF1B inhibits tumor progression and enhances efficacy of cisplatin in pancreatic cancer.Cancer biomarkers : section A of Disease markers · 2022Article
- A regulatory phosphorylation site on Mec1 controls chromatin occupancy of RNA polymerases during replication stress.The EMBO journal · 2021Article
- Transcription-Replication Collisions-A Series of Unfortunate Events.Biomolecules · 2021Review
- Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity.Science advances · 2021Article
- Epigenetics in prostate cancer treatment.Journal of translational genetics and genomics · 2021Article
- The OTUD5-UBR5 complex regulates FACT-mediated transcription at damaged chromatin.Nucleic acids research · 2019Article
- Maintenance of genome stability: the unifying role of interconnections between the DNA damage response and RNA-processing pathways.Current genetics · 2018Review
- Review
- BMI1-UBR5 axis regulates transcriptional repression at damaged chromatin.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Transcription-replication conflicts: how they occur and how they are resolved.Nature reviews. Molecular cell biology · 2016Review
- Article
- ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition.Cell reports · 2015Article
- Review
- Fitness profiling links topoisomerase II regulation of centromeric integrity to doxorubicin resistance in fission yeast.Scientific reports · 2015Article
- Cell cycle-dependent changes in H3K56ac in human cells.Cell cycle (Georgetown, Tex.) · 2015Article
- End of the beginning: elongation and termination features of alternative modes of chromosomal replication initiation in bacteria.PLoS genetics · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Many agents used for chemotherapy, such as doxorubicin, interfere with DNA replication, but the effect of this interference on transcription is largely unknown. Here we show that doxorubicin induces the firing of dense clusters of neoreplication origins that lead to clusters of stalled replication forks in gene-rich parts of the genome, particularly on expressed genes. Genes that overlap with these clusters of stalled forks are actively dechromatinized, unwound, and repressed by an ATR-dependent checkpoint pathway. The ATR checkpoint pathway causes a histone chaperone normally associated with the replication fork, ASF1a, to degrade through a CRL1(βTRCP)-dependent ubiquitination/proteasome pathway, leading to the localized dechromatinization and gene repression. Therefore, a globally active checkpoint pathway interacts with local clusters of stalled forks to specifically repress genes in the vicinity of the stalled forks, providing a new mechanism of action of chemotherapy drugs like doxorubicin. Finally, ASF1a-depleted cancer cells are more sensitive to doxorubicin, suggesting that the 7%-10% of prostate adenocarcinomas and adenoid cystic carcinomas reported to have homozygous deletion or significant underexpression of ASF1a should be tested for high sensitivity to doxorubicin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.